Inflammation and injury to the kidney is usually a product of complex biochemical events. These events initiate and provide dynamic conduits for the calamitous progression towards end-stage kidney disease in humans. We believe that a better comprehension of the proximal mechanisms underlying these interlocking and destructive processes may offer new insights leading to the formation of rational strategies for improved treatment. The major theme of our Renal Center focuses, therefore, on the engagement of fundamental molecular mechanisms which detrimentally facilitate the development of parenchymal Injury and Its extended consequences to target structures and somatic cells along the nephron. Our research will examine several different categories of interactions in a series of new and provocative studies. These projects will collectively bridge the disciplines of genetics and biochemistry with basic pathophysiology in order to better evaluate events preceding the aberrant structural change of renal tissue. This grant will support nine academic scientists located physically in one comprehensive research facility consisting of thirty-eight individual experimental work stations surrounding a common core area containing large equipment, and providing space for nucleic acid sequencing and tissue culture. Our Renal Center will be composed initially of four major research projects and three core units: Project 1 will use molecular and cellular techniques to determine the mechanisms by which glomerular injury produces subsequent tubulointerstitial inflammation; Project 2 will focus on the molecular determinants and biologic consequences of nuclear localization of anti-DNA antibodies in renal cells; Project 3 will investigate the molecular and biochemical factors which induce renal cell growth and hypertrophy in diabetes mellitus; and Project 4 will study the molecular mechanisms by which regulatory T cells mediate a specific and highly targeted downregulation of autoimmune renal injury. Core units for tissue cell culture, for oligonucleotide synthesis and nucleic acid sequencing, and for project administration will be established as part of the supportive infrastructure. Our Renal Center will also serve as a regional resource for the tertiary care of renal patients with various forms of inflammatory kidney damage.